Journal
PLOS ONE
Volume 8, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0079565
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Funding
- National Health Medical Research Council (NHMRC)
- Hunter Medical Research Institute
- Hunter Children's Research Foundation
- NH&MRC Health Professional Research Fellowship
- CAPES
- CNPq
- FAPEMIG
- Asthma UK [CH1155]
- MRC Centre grant [G1000758]
- ERC [233015]
- European Research Council (ERC) [233015] Funding Source: European Research Council (ERC)
- MRC [G1000758] Funding Source: UKRI
- Medical Research Council [G1000758] Funding Source: researchfish
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Background: Severe asthma is associated with T helper (T-H) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro. Objective: To determine the anti-inflammatory potential of anthraquinones in-vivo. Methods: BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation. Results: Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor expression, and ameliorated allergen-and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of T(H)2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung. Conclusion: Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.
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